Variant chr7-19117047-CCGCCGCCGCCGCCCG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BS1BS2

The NM_000474.4(TWIST1):c.260_274del(p.Ala87_Gly91del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000108 in 1,398,748 control chromosomes in the GnomAD database, including 8 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00031 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000084 ( 7 hom. )

Consequence

TWIST1
NM_000474.4 inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.49

Variant links:

Genes affected

TWIST1 (HGNC:12428): (twist family bHLH transcription factor 1) This gene encodes a basic helix-loop-helix (bHLH) transcription factor that plays an important role in embryonic development. The encoded protein forms both homodimers and heterodimers that bind to DNA E box sequences and regulate the transcription of genes involved in cranial suture closure during skull development. This protein may also regulate neural tube closure, limb development and brown fat metabolism. This gene is hypermethylated and overexpressed in multiple human cancers, and the encoded protein promotes tumor cell invasion and metastasis, as well as metastatic recurrence. Mutations in this gene cause Saethre-Chotzen syndrome in human patients, which is characterized by craniosynostosis, ptosis and hypertelorism. [provided by RefSeq, Jul 2020]

TWIST1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1

In a chain Twist-related protein 1 (size 201) in uniprot entity TWST1_HUMAN there are 62 pathogenic changes around while only 11 benign (85%) in NM_000474.4

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000307 (46/150060) while in subpopulation AFR AF= 0.00101 (42/41386). AF 95% confidence interval is 0.000771. There are 1 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TWIST1	NM_000474.4 linkuse as main transcript	c.260_274del	p.Ala87_Gly91del	inframe_deletion	1/2	ENST00000242261.6
TWIST1	NR_149001.2 linkuse as main transcript	n.575_589del		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TWIST1	ENST00000242261.6 linkuse as main transcript	c.260_274del	p.Ala87_Gly91del	inframe_deletion	1/2	1	NM_000474.4	P1
TWIST1	ENST00000354571.5 linkuse as main transcript	c.57_71del	p.Ala20_Gly24del	inframe_deletion, NMD_transcript_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.000307

AC:

AN:

149952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000203

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000365

AC:

AN:

49264

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

29172

show subpopulations

Gnomad AFR exome

AF:

0.00820

Gnomad AMR exome

AF:

0.000882

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000419

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000129

Gnomad OTH exome

AF:

0.000697

GnomAD4 exome

AF:

0.0000841

AC:

105

AN:

1248688

Hom.:

AF XY:

0.0000848

AC XY:

AN XY:

613002

show subpopulations

Gnomad4 AFR exome

AF:

0.00225

Gnomad4 AMR exome

AF:

0.000321

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000355

Gnomad4 SAS exome

AF:

0.0000359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000354

Gnomad4 OTH exome

AF:

0.0000779

GnomAD4 genome

AF:

0.000307

AC:

AN:

150060

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

AN XY:

73240

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.0000662

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000204

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000297

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over